Adhesion of cells to a supporting substrata is of a fundamental importance for normal cell behavior. Studies in our laboratory have shown that the cell substrate adhesion process can be divided into different discrete stages. After cells have attached and spread on a physiological substratum, they will in many cases develop specialized matrix contacts (e.g. focal adhesions and reorganize their cytoskeletal elements to form stress fibers. Formation of focal adhesions in mesenchymal cells seeded on a fibronectin substratum seems to depend on the presence of a cell associated heparan sulfate proteoglycan that interacts via its polysaccharide chains with glycosaminoglycan binding domains in the fibronectin molecule. These observations form the basis for the current proposal. Answers to the following questions will be sought: What are the structural requirements of substrate molecules other than fibronectin (e.g. laminin and fibrinogen) for promoting focal adhesion and stress fiber formation? What is the structure of the core protein of cell surface heparan proteoglycan and how is it anchored in the membrane? How are membrane bound heparan sulfate proteoglycans associated with cytoskeletal components? Does focal adhesion formation result in post- translational modification such as phosphorylation of participating proteins? How is cell substrate adhesion process regulated? In these studies, we will use biochemical, cell biological, molecular genetical and immunological techniques. It is our belief that answers to these questions would help us better understand the basic cellular processes involved in normal and pathological tissue remodeling and repair.